In a year-long open-label study of 802 adults with treatment-resistant depression, esketamine nasal spray combined with a new oral antidepressant showed a manageable safety profile and sustained improvement in depressive symptoms. Common side effects included dizziness, dissociation, nausea, and headache, mostly mild or moderate and resolving the same day. Two deaths occurred, neither linked to the drug. Cognitive performance remained stable or improved. Depression scores dropped during the first four weeks and stayed lower through the maintenance phase.
Adults with treatment-resistant depression who continued esketamine nasal spray plus an oral antidepressant in a long-term extension study (SUSTAIN-3) showed sustained improvement in depression ratings over up to 4.5 years. Among 1148 participants, common side effects included headache, dizziness, nausea, dissociation, somnolence, and nasopharyngitis. Depression scores dropped during the initial four-week induction phase and remained low during maintenance; about 46% of participants were in remission at the maintenance phase endpoint. No new safety concerns emerged with long-term, intermittent dosing.